<p>Different theoretical developments in Cultural Psychology have advanced the understanding of the semiotic mediation of human experience, with particular emphasis on how cognition and affect are intertwined. Simultaneously, the application of Cultural Psychology to health contexts remains notably less developed, particularly in relation to the study of conditions involving multiple therapeutic demands within medical treatment. In this context, the present study aims to understand the configuration of the experience of medical treatment in Type 1 Diabetes Mellitus through the analysis of the organization, regulation, and interaction of affective semiosis and meaning-making processes. Methodologically, an idiographic perspective was adopted through the microgenetic analysis of in-depth interviews within a case study. The analysis is developed through the use of metaphors, understood as semiotic configurations that articulate the experience of the Self. A central metaphor, “the daily roulette”, and four peripheral metaphors serving structuring and operational functions were identified. Results show that experience is organized around an affective field of contingency that guides the interpretation of bodily variations. Processes of meaning-making are identified as operating through micro-stabilizations of meaning making orienting action in concrete situations. The study deepens the theoretical understanding of the articulation between the body, affective semiosis, and meaning-making, suggesting specific properties of signs regulation of experience. Within Cultural Psychology applied to the field of health, it also offers insights into how individuals regulate their experience of treatment in contexts of bodily uncertainty, thereby informing the development of approaches more attuned to patients’ affective dynamics.</p>